Tofranil

CLINICAL PHARMACOLOGY

The mechanism of action of Tofranil is not definitely
known. However, it does not act primarily by stimulation of the central nervous
system. The clinical effect is hypothesized as being due to potentiation of
adrenergic synapses by blocking uptake of norepinephrine at nerve endings. The
mode of action of the drug in controlling childhood enuresis is thought to be
apart from its antidepressant effect.

Animal Pharmacology & Toxicology

A. Acute: Oral LD50 ranges are as follows:

Rat 355 to 682 mg/kg
Dog 100 to 215 mg/kg

Depending on the dosage in both species, toxic signs
proceeded progressively from depression, irregular respiration and ataxia to
convulsions and death.

B. Reproduction/Teratogenic: The overall evaluation may be
summed up in the following manner:

Oral: Independent studies in three species (rat, mouse,
and rabbit) revealed that when Tofranil is administered orally in doses up to
approximately 2-½ times the maximum human dose in the first 2 species and up
to 25 times the maximum human dose in the third species, the drug is
essentially free from teratogenic potential. In the three species studied, only
one instance of fetal abnormality occurred (in the rabbit) and in that study there
was likewise an abnormality in the control group. However, evidence does exist from
the rat studies that some systemic and embryotoxic potential is demonstrable.
This is manifested by reduced litter size, a slight increase in the stillborn
rate, and a reduction in the mean birth weight.

Last reviewed on RxList: 9/17/2014
This monograph has been modified to include the generic and brand name in many instances.